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Cerebellar development and its mediation role in cognitive planning in childhood.

ABSTRACT: Recent evidence suggests that the cerebellum contributes not only to the planning and execution of movement but also to the high-order cognitive planning. Childhood is a critical period for development of the cerebellum and cognitive planning. This study aimed (a) to examine the development of cerebellar morphology and microstructure and (b) to examine the cerebellar mediation roles in the relationship between age and cognitive planning in 6- to 10-year-old children (n?=?126). We used an anatomical parcellation to quantify cerebellar regional gray matter (GM) and white matter (WM) volumes, and WM microstructure, including fractional anisotropy (FA) and mean diffusivity (MD). We assessed planning ability using the Stockings of Cambridge (SOC) task in all children. We revealed (a) a measure-specific anterior-to-posterior gradient of the cerebellar development in childhood, that is, smaller GM volumes and greater WM FA of the anterior segment of the cerebellum but larger GM volumes and lower WM FA in the posterior segment of the cerebellum in older children; (b) an age-related improvement of the SOC performance at the most demanding level of five-move problems; and (c) a mediation role of the lateral cerebellar WM volumes in age-related improvement in the SOC performance in childhood. These results highlight the differential development of the cerebellum during childhood and provide evidence that brain adaptation to the acquisition of planning ability during childhood could partially be achieved through the engagement of the lateral cerebellum.

SUBMITTER: Kipping JA

PROVIDER: S-EPMC6866433 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Cerebellar development and its mediation role in cognitive planning in childhood.

Kipping Judy A JA Xie Yingyao Y Qiu Anqi A

Human brain mapping 20180822 12

Recent evidence suggests that the cerebellum contributes not only to the planning and execution of movement but also to the high-order cognitive planning. Childhood is a critical period for development of the cerebellum and cognitive planning. This study aimed (a) to examine the development of cerebellar morphology and microstructure and (b) to examine the cerebellar mediation roles in the relationship between age and cognitive planning in 6- to 10-year-old children (n = 126). We used an anatomi ...[more]

PMID: 30133063

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Project description:UnlabelledPax6 is a prominent gene in brain development. The deletion of Pax6 results in devastated development of eye, olfactory bulb, and cortex. However, it has been reported that the Pax6-null Sey cerebellum only has minor defects involving granule cells despite Pax6 being expressed throughout cerebellar development. The present work has uncovered a requirement of Pax6 in the development of all rhombic lip (RL) lineages. A significant downregulation of Tbr1 and Tbr2 expression is found in the Sey cerebellum, these are cell-specific markers of cerebellar nuclear (CN) neurons and unipolar brush cells (UBCs), respectively. The examination of Tbr1 and Lmx1a immunolabeling and Nissl staining confirmed the loss of CN neurons from the Sey cerebellum. CN neuron progenitors are produced in the mutant but there is an enhanced death of these neurons as shown by increased presence of caspase-3-positive cells. These data indicate that Pax6 regulates the survival of CN neuron progenitors. Furthermore, the analysis of experimental mouse chimeras suggests a cell-extrinsic role of Pax6 in CN neuron survival. For UBCs, using Tbr2 immunolabeling, these cells are significantly reduced in the Sey cerebellum. The loss of UBCs in the mutant is due partly to cell death in the RL and also to the reduced production of progenitors from the RL. These results demonstrate a critical role for Pax6 in regulating the generation and survival of UBCs. This and previous work from our laboratory demonstrate a seminal role of Pax6 in the development of all cerebellar glutamatergic neurons.Significance statementPax6 is a key molecule in development. Pax6 is best known as the master control gene in eye development with mutations causing aniridia in humans. Pax6 also plays important developmental roles in the cortex and olfactory bulb. During cerebellar development, Pax6 is robustly expressed in the germinal zone of all glutamatergic neurons [cerebellar nuclear (CN) neurons, granule cells, and unipolar brush cells (UBCs)]. Past work has not found abnormalities in the CN and UBC populations. Our study reveals that the Pax6-null mutation dramatically affects these cells and identifies Pax6 as a key regulator of cell survival in CN neurons and of cell production in UBCs. The present study shows how Pax6 is key to the development of glutamatergic cells in the cerebellum.

Dataset Information

Cerebellar development and its mediation role in cognitive planning in childhood.

Publications

Cerebellar development and its mediation role in cognitive planning in childhood.

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